Ka ʻOihana Olakino

TANDEM MASS SPECTROMETRY PROJECT

Tandem Mass Spectrometry (MS/MS) Research Project
Fact Sheet for Pediatric Care Providers
Background Information

The introduction of Tandem Mass Spectrometry (MS/MS) in the 1990s for population-based newborn screening has enabled health-care providers to detect an increased number of metabolic disorders in a single process by using dried blood spot specimens routinely collected for newborn screening. MS/MS allows for screening of multiple metabolic disorders using a single analytical run. With this technology there is the potential to test for a wide array of metabolic disorders, including amino acid disorders, organic acidemias, and fatty acid oxidation disorders (see list of disorders). Because the technology can detect these disorders (approximately 30 total) within 1 to 2 minutes, the system can handle the large numbers of specimens required in newborn screening.

For some of the disorders identifiable via MS/MS, such as medium chain acyl-CoA dehydrogenase deficiency (MCAD), early detection and treatment can result in substantial improvements in health outcomes (i.e., prevention of mortality and improvement of the quality of life). Several states have already expanded, or are in the process of expanding, their newborn screening program to add these disorders.

The Department of Health Hawaii Newborn Metabolic Screening Program (NBMSP) has been in existence since 1986 and currently tests for PKU, galactosemia, congenital hypothyroidism, congenital adrenal hyperplasia, maple syrup urine disease, biotinidase deficiency, and hemoglobinopathies.

The California Department of Health Genetics Disease Branch received a grant in June 2001 from the Health Resources and Services Administration to conduct a pilot study MS/MS newborn screening. Since California and Hawai`i have a long history of collaboration, the Hawaii Department of Health NBMSP was invited to participate in the pilot study. Due to limited funding, the pilot study will be limited to newborns in Kapiolani Medical Center for Women and Children (KMCWC).

Overview of the NBS MS/MS Research Project

This study is being conducted in part to determine which of the disorders identifiable via MS/MS meet the criteria for inclusion in Hawaii’s mandatory Newborn Metabolic Screening Program, i.e., which of the unusual results have clinical significance and/or warrant reporting. Almost all “interesting” or “unusual” results will be reported out to the primary care provider and follow-up and evaluation will be provided by the Hawaii NBMSP or its project consultants. Treatment and outcome data will be collected on all newborns with interesting or unusual screening results. The estimated duration of the supplemental testing is March 1 – December 31, 2002. Participation in the study will be voluntary and informed consent will be obtained for both the testing of specimens. There will be no additional fee charged for participation in the supplemental screening. Based upon 6,000 annual births at KMCWC and an acceptance rate similar to other states that have offered MS/MS supplemental screening, we are projecting that up to 4,500 newborns being screened via MS/MS during the pilot period. We anticipate detecting 1-2 newborns with clinically significant metabolic disorders currently that are not detected through the mandatory newborn screening program.

Role of Pediatric Care Providers

Pediatric Care Providers should be knowledgeable about the supplemental screening program, be available to answer questions, and provide additional information to parents. Also, pediatric care providers should report and follow up on any unusual signs and symptoms observed while a child is in their care even if the newborn screen is normal.All diagnosed cases of metabolic disorders identifiable via MS/MS in newborn period (see list of disorders) should be reported to the Department of Health NBMSP whether disorders were detected via screening or not.

Reporting of Screening Results

Hospitals and the pediatric care providers listed on the Newborn Metabolic Screening Specimen Collection Form will continue to receive a written report on the mandatory screening program. However, during the research project, hospitals will not receive results on the supplemental screening. Only “unusual results” of the supplemental screening will be reported, and the report will go to the pediatric care provider listed on the Specimen Collection Form. To expedite the process of follow-up of newborn screening results for both the mandatory and supplemental programs, hospital staff completing the Specimen Collection Form need to enter the correct name and address of the pediatric care provider who will be following each newborn after hospital discharge (the newborn’s “medical home”). Pediatric care providers should make sure that the hospital has the correct information.

Follow-up for Unusual Results

For newborns with unusual results, the pediatric care provider will be contacted via telephone by the NBMSP Coordinator,  Follow-up and evaluation of the newborns by the metabolic clinic and consultants will be coordinated by NBMSP Coordinator. Based upon the experience of the research project and input from the metabolic specialists, follow-up guidelines for these conditions will be developed.

Key Points to Emphasize with Parents

• No additional blood will be taken from the newborn.
• Knowledge gained from this project will be used to expand the program in the future to improve screening for newborns and families.
• All disorders may not be detectable, i.e., there will probably be disorders that are missed since this is only screening.
• There could be some benefit to families who participate e.g., early detection and treatment for newborns with one of the disorders.
• Negative supplemental screening results will not be reported to the pediatrician.
• If a specimen is inadequate, the supplemental testing will not be run and parents will not be offered repeat supplemental testing through the program.
• If there is a family history of metabolic disorders or if the family has concerns, they should be offered information on obtaining supplemental testing outside of, or in addition to, the research study. Optional supplemental screening is offered for a fee by Baylor University Medical Center, Dallas, Texas (https://www.baylordallas.edu), or Pedrix Medical Group, Bridgeville, Pennsylvania (https://www.pediatrix.com).
• There is no additional cost for the voluntary supplemental screening test.
• Any required follow-up screening and/or confirmatory tests will be covered by the Hawaii NBMSP.
• Treatment services are not covered by NBMSP. However, the patient’s health insurance, Medicaid or the Children with Special Health Needs Program may pay for these services.

Who are the investigators for this project?

PRINCIPAL INVESTIGATOR:
Sylvia Au, M.S., C.G.C.
Hawaii State Genetics Coordinator,
Children with Special Health Needs Branch

CO-INVESTIGATORS:

Christine A. Matsumoto, R.N., M.P.H., Newborn Metabolic Screening Program Coordinator
Venkataraman Balaraman, M.D., Neonatologist, Kapiolani Medical Center for Women and Children
Sorrell Waxman, M.D., Pediatric Endocrinologist, Kapiolani Medical Center for Women and Children
Patricia Heu, M.D., M.P.H., Chief, Children with Special Health Needs Branch, Department of Health

Additional Information

The parent brochure entitled, “More Information About Supplemental Newborn Screening”, explains the supplemental research testing. Providers or patients who have questions can call the NBMSP Coordinator at 733-9069 for additional information.